scholarly journals Molecular Docking for Ligand-Receptor Binding Process Based on Heterogeneous Computing

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Jianhua Li ◽  
Guanlong Liu ◽  
Zhiyuan Zhen ◽  
Zihao Shen ◽  
Shiliang Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Receptor Binding ◽  
Distributed Memory ◽  
Memory System ◽  
Parallel Program ◽  
Coarse Grained ◽  
Flexible Docking ◽  
Binding Process ◽  
Parallel Scheme ◽  
Computationally Intensive

Molecular docking aims to predict possible drug candidates for many diseases, and it is computationally intensive. Particularly, in simulating the ligand-receptor binding process, the binding pocket of the receptor is divided into subcubes, and when the ligand is docked into all cubes, there are many molecular docking tasks, which are extremely time-consuming. In this study, we propose a heterogeneous parallel scheme of molecular docking for the binding process of ligand to receptor to accelerate simulating. The parallel scheme includes two layers of parallelism, a coarse-grained layer of parallelism implemented in the message-passing interface (MPI) and a fine-grained layer of parallelism focused on the graphics processing unit (GPU). At the coarse-grain layer of parallelism, a docking task inside one lattice is assigned to one unique MPI process, and a grouped master-slave mode is used to allocate and schedule the tasks. Meanwhile, at the fine-gained layer of parallelism, GPU accelerators undertake the computationally intensive computing of scoring functions and related conformation spatial transformations in a single docking task. The results of the experiments for the ligand-receptor binding process show that on a multicore server with GPUs the parallel program has achieved a speedup ratio as high as 45 times in flexible docking and as high as 54.5 times in semiflexible docking, and on a distributed memory system, the docking time for flexible docking and that for semiflexible docking gradually decrease as the number of nodes used in the parallel program gradually increases. The scalability of the parallel program is also verified in multiple nodes on a distributed memory system and is approximately linear.

scholarly journals Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1051
Author(s):  
Edgardo Becerra ◽  
Giovanny Aguilera-Durán ◽  
Laura Berumen ◽  
Antonio Romo-Mancillas ◽  
Guadalupe García-Alcocer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Binding Sites ◽  
Adenosine Monophosphate ◽  
Competitive Inhibitor ◽  
Umbrella Sampling ◽  
Coarse Grained ◽  
Nucleotide Polymorphisms

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.

Discovery of potential inhibitors of the receptor-binding domain (RBD) of pandemic disease-causing SARS-CoV-2 Spike Glycoprotein from Triphala through molecular docking

2021 ◽  
Vol 01 ◽  
Author(s):  
Sharuk L. Khan ◽  
Falak A. Siddiqui ◽  
Mohd Sayeed Shaikh ◽  
Nitin V. Nema ◽  
Aijaz A. Shaikh
Keyword(s):  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Receptor Binding ◽  
Chemical Constituents ◽  
Antioxidant Properties ◽  
Binding Domain ◽  
Quality Data ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein

Background: COVID-19 (SARS-CoV-2 infection) has affected almost every region of the world. Presently, there is no defined line of treatment available for it. Triphala is already proven to have a safe biological window and well known for its antioxidant and immunomodulatory properties. Objective: Present work has been carried out to study Triphala's effectiveness for the treatment of COVID-19. Methods: The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein responsible for the invasion into the host cell, which leads to further infection. The molecular docking (MD) was performed to explore the binding affinities (kcal/mol) of Triphala's chemical constituents and compared them with the existing drugs under investigation for the treatment of COVID-19 epidemiology. Results: Chebulinic acid binding affinity -8.5 kcal/mol with the formation of 10 hydrogen bonds. Almost all the major chemical constituents have formed two or more hydrogen bonds with RBD of SARS-CoV-2 Spike Glycoprotein. Conclusion: The present study showed that Triphala might perform vital roles in the treatment of COVID-19 and expand its usefulness to physicians to treat this illness. There is a need to complete the in-vitro, in-vivo biological testing of Triphala on SARS-CoV-2 disease to create more quality data. The binding mode of Chebulinic acid in the allosteric cavity allows a better understanding of RBD of SARS-CoV-2 Spike Glycoprotein target and provides insight for the design of new inhibitors. Triphala is already proven to have a safe biological window, which indicates we can skip the pre-clinical trials. Apart from this, Triphala is well known for its antioxidant properties, which ultimately improves the immunity of the COVID-19 patient.

Parallel rendering of radiance on distributed memory system by PVM

1997 ◽  
pp. 502-507
Author(s):  
E. García Salcines ◽  
G. Cerruela García ◽  
J. I. Benavides Benítez ◽  
F. Muñoz García ◽  
E. Sáez Peña
Keyword(s):  
Distributed Memory ◽  
Memory System ◽  
Parallel Rendering
Sign in / Sign up

Export Citation Format

Share Document